Reflecting time-of-flight (ToF) mass spectrometers are well known in the art. They are provided commercially for a wide range of applications, including analysis of organic substances such as pharmaceutical compounds, environmental compounds and bio molecules, including DNA and protein sequencing. In such applications, there is increasing demand for high mass accuracy, high resolution, high sensitivity and analysis speed that is compatible with gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS).
The mass resolving power of a ToF analyser may be improved by ensuring that ions of different mass to charge (m/z) values arrive at the detector spaced apart in time and that ions of a single mass to charge (m/z) value arrive at the detector as closely spaced in time as possible. It is known that the mass resolving power achieved by a reflecting time of flight mass spectrometer may be improved by lengthening the flight path. This may be done by the introduction of a Multi-reflecting ion mirror as described in WO2005/001878 or, alternatively, by providing periodic field variation in the drift direction inside planar mirrors as described in WO 2010/008386. Alternatively US 2009/0314934, US 2010/0148061 and Satoh, et al. in J. Am. Soc. Mass Spectrom. 18, 1318-1323, 2007 describe ToF systems having a series of sector fields. These systems are now realised in practice as commercially available ToF systems and can deliver mass resolving powers in the region 50 to 100 k as described by Patrick et al in GC/LC ChromatographyOnline.COM (1 May 2011) and Satoh, et al, in J. Am. Soc. Mass. Spectrom (2011) 22:797-803.
A single ToF analyser is a system in which ions undergo a single reflection from a single ion mirror. Such a system is the most commonly employed and is well known in the art of time-of-flight mass spectrometry and many examples are provided commercially. In such systems the flight path may be increased simply by increasing the distance, l, between the ion mirror and the ion source as described in International Journal of Mass Spectrometry 210/211 (2001) 89-100.
Attempts have been made to improve the duty cycle, resolving power, scan speed and mass range of time of flight mass spectrometers by using different ion sources to introduce ions into a time of flight mass spectrometer. For example, ion traps have been used for storing and preparing ions prior to their injection along a flight axis, the technique being known as Trap-ToF. There are several types of ion trap that can be used in Trap-ToF. The first instrument in this class was described by S. Michael et al., in Rev. Sci. Instrum., 1992, 63, 4277-4284, in U.S. Pat. No. 5,569,917, and in U.S. Pat. No. 5,763,878. Therein is described the use of a 3D quadrupole ion trap as an accumulator and injector into a ToF mass analyser. This type was implemented very successfully, however, the 3D quadrupole ion trap has a limited capacity for ion cloud storage, and mass range and scan speed is limited. An improvement in capacity for ion cloud storage may be gained by employing Linear ion traps or Curved ion traps, which provide an increase in the volume of ion cloud and thus increase the number of ions which can be trapped before space charge effects start to affect performance.
Franzen described an ion trap comprising parallel straight rods with ion ejection orthogonal to the rods, in U.S. Pat. No. 5,763,878. Makarov et al. describe a curved multipole rod trap with orthogonal ejection, in U.S. Pat. No. 6,872,938, and an elongated ion trap with no uniform inscribed radius along the axis was described in WO2008/081334, which was also aimed at improving the ion trap capacity. An improved method of injecting ions from an ion trap to ToF analyser was described in US2008/0035842 by employing a digital method for providing the trapping waveform, and methods to introduce ions to an ion storage trap with reduced inscribed radius was described in US2010/072362 by Giles et al. This reduction in inscribed radius is advantageous because the ion cloud within the ion trap can be made smaller and the extraction field can be made higher; both measures may provide improvement of the final mass resolving power.
In an Orthogonal-ToF (O-ToF) ions are extracted from a field free region external to the ion guide, which is the most common method of introducing ions to ToF analysers. The Orthogonal extraction method was the first method to adapt an ion beam from a continuous ion source into a pulsed ion beam necessary for a time of flight analyser: sections of the beam are pulsed in a direction orthogonal to the continuous beam. This method is commonly known as an “orthogonal Time of flight mass spectrometer” (OToF) and it is based on the original work of Wiley & McLaren in 1955 (“Time-of-Flight Mass Spectrometer with Improved Resolution”, Rev. Sci. Instrum. 26, 1150-1157 (1955)).
There have been a number of methods for focusing ions into the pulsing region to improve resolving power, for example Boyle et al., in C. M. Anal. Chem. 1992, 64, 2084. However, the duty cycle is much lower than in the Trap-ToF method due to the duty cycle at which the continuous beam may be converted to the pulsed beam. Additionally, a proportion of ions are lost by deliberate cuffing/reduction of the ion beam to achieve a desired initial velocity and spatial distribution. Using such methods Orthogonal ToF systems have in recent years achieved mass resolving power of 35 to 40 k. This is the state of the art in current commercial systems. O-ToF is usually coupled to a two-stage reflectron. The main disadvantage of Orthogonal-ToF systems is the limitation imposed by the flight time of ions from the ion guide region to pulsing region. There have recently been a number of attempts to address the problem of the poor duty cycle of the O-ToF, see for example GB2391697 and CA 2349416 (A1), however the efficiency is still not as high as can be achieved by Trap-ToF methods.
It is known that ion sources produce ions with a range of energies. The spread of ion energies, for ions of a given mass to charge ratio (m/z ratio), places a limit on the resolving power of a ToF mass analyser. U.S. Pat. No. 6,518,569 describes how ion mirrors used in reflecting time of flight mass spectrometers can be configured to improve resolving power by providing energy focusing of the ion cloud. In general ion mirrors can be divided into two groups, linear and non-linear, according to the distribution of the electric field within the ion mirror. It has been demonstrated that non-linear ion mirrors can achieve higher resolution than linear ion mirrors (Cornish, T. J. et al., Rapid Commun. Mass Spectrom., 8, 781-785 (1994)). WO03/103008 notes that an ion beam of finite diameter entering a non-linear ion mirror in a mass spectrometer will experience a range of non-linear electric fields and this reduces the resultant resolving power and laterally disperses the ion beam. However, WO03/103008 makes no suggestion as how to reduce this problem.
U.S. Pat. No. 6,518,569 states that in contrast to a linear ion mirror, a non-linear ion mirror has an electric field contour that is curved along its axis; in an ideal non-linear ion mirror the electric field should take the theoretically optimum contour along the mirror axis and an absolutely homogeneous field in the off-axis directions. This document also notes the problem that any inhomogeneity in the off-axis direction results in ion dispersion away from the ion beam centre and an inequality in flight time across an ion beam of finite width. This document suggests reducing off-axis inhomogeneity to ensure that all ions within a beam of finite width experience the same axial field.